Thymic atrophy and the progressive immune decline that accompanies it is a major health problem, chronically with age and acutely with immune injury. No definitive solution is available. Here we demonstrate that one of the three mesenchymal cell subsets identified by single-cell analysis of human and mouse thymic stroma is a critical niche component for T lymphopoiesis. The Postn+ subset is perivascular, and its depletion abrogates T cell progenitor recruitment, likely through production of the chemokine Ccl19. It markedly declines with age and in the acute setting of hematopoietic stem cell transplant conditioning. When isolated and adoptively transferred, Postn+ cells durably engraft the atrophic thymus, recruit early T progenitors, increase T cell neogenesis and enhance T cell response to vaccination. More readily available mesenchymal populations expressing Ccl19 provide similar effects. These data define a thymus lymphopoietic niche cell type that may be manipulated therapeutically to regenerate T lymphopoiesis.
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This may be old news, but I found this study on Rapamycin’s effect on the thymus encouraging. We have known that Rapa involutes the thymus of transplant patients, but short term intermittent use actually causes the thymus to rebound better than before—at least in mice.
Kinetics of thymic regeneration in female mice following short-term rapamycin administration
These results demonstrate that RAPA triggers transient thymic suppression followed by thymus volume and functional recovery. It seems that RAPA-mediated immune reconstitution may be an important reason for the potential anti-aging effect of RAPA.
https://www.sciencedirect.com/science/article/abs/pii/S0014299925007149
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That paper is only from Sept. 2025 - and I had not seen it. Good find. Paper out of China, but still very interesting.
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